Objective:To explore the effects of coenzyme Q10(CoQ10) on high-fat diet-induced obesity, lipid disorders, and bile acid metabolism in mice.Methods:Eight-week-old C57BL/6J mice were randomly divided into control group(regular chow), high-fat diet group(45% high-fat chow), and CoQ10 intervention group(45% high-fat chow+ 100 mg·kg -1·d -1CoQ10) based on their body weights according to the randomized block design. The body weight and food intake of mice in each group were collected. The levels of serum total cholesterol, triglyceride, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol, alanine aminotransferase, and aspartate aminotransferase were detected. The contents of 17 bile acids in serum, liver, and colon contents of mice were detected by ultra-performance liquid chromatography-tandem mass(UPLC-MS/MS). The protein expressions of cholesterol 12α-hydroxylase(CYP8B1) and oxysterol 7α-hydroxylase(CYP7B1) in liver were detected by Western blotting. Results:CoQ10 significantly reduced body weight and ameliorated lipid metabolism disorders in mice fed a high-fat diet. Compared with the control group, serum total bile acid levels were reduced in the high-fat diet group( P<0.05); CoQ10 intervention elevated serum and colonic total bile acid levels( P=0.021, P=0.014) and increased liver, colon, and serum deoxycholic acid and ursodeoxycholic acid levels( P<0.05) in the mice compared with the high-fat diet group. Both colonic and serum deoxycholic acid levels in the CoQ10 intervention group were negatively correlated with body weights( P=0.024, P=0.019), and colonic deoxycholic acid and total cholesterol levels were also negatively correlated( P=0.006). CoQ10 increased the expression of CYP8B1 and CYP7B1 proteins in the liver of mice. Conclusion:CoQ10 can modulate bile acid metabolism in high-fat diet-fed mice and alleviate their obesity and lipid metabolism disorders.

Objective:To explore the value of serum matrix metalloproteinase-1 (matrix metalloproteinase-1), and phosphatase and tensin hmmlogydeleted on ten (PTEN), in predicting osteoporosis (OP) in women with gestational diabetes mellitus (GDM) .Methods:The clinical data of.218 pregnant women with GDM treated in Linyi People’s Hospital from Sep. 2019 to Feb. 2023 were retrospectively collected and included in the GDM group. Another 98 healthy pregnant women who underwent physical examination during the same period were selected as the control group. Age, body mass index (BMI), blood glucose related indexes and serum MMP-1 and PTEN levels were compared between the two groups. According to the occurrence of osteoporosis (OP) in the second and third trimester of pregnancy, the GDM group was divided into OP group and non-OP group. Logistic regression analysis was used to explore the influencing factors of OP in pregnant women with GDM in the second and third trimesters. ROC curve was drawn to analyze the predictive value of serum MMP-1 and PTEN levels for osteoporosis in GDM pregnant women in the second and third trimesters.Results:Body mass index (BMI), fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c) and serum MMP-1 and PTEN levels in GDM group were higher than those in control group, but BUA, SOS and SI were lower than those in control group ( t=6.18, 12.68, 9.91, 11.42, 7.70, 5.63, 5.76, 9.84, all P<0.05). Among 218 GDM women, 29 cases had OP and 189 cases did not have OP. There were no significant differences in fasting blood glucose, glycosylated hemoglobin, blood calcium, blood magnesium, or blood phosphorus between the two groups (statistical value: 0.96, 0.86, 1.35, 1.06, 0.49, P>0.05). Logistic regression analysis showed that age, abnormal increase of MMP-1 and PTEN levels were independent risk factors for OP in GDM women in the second and third trimesters [ OR (95% CI) =1.260 (1.103-1.440) ,1.075 (1.031-1.120) ,1.055 (1.023-1.089), all P<0.05]. ROC curve showed that the AUC of MMP-1 and PTEN in predicting OP in GDM pregnant women in the second and third trimesters were 0.824 and 0.777, respectively. The AUC of the combination of the two in predicting OP in GDM pregnant women in the second and third trimesters was 0.933, and the specificity and sensitivity were 83.04% and 93.48%, respectively, which were higher than those of single detection. Conclusions:MMP-1 and PTEN in early pregnancy may play a potential role in the prediction of OP in pregnant women with GDM. Close monitoring of MMP-1 and PTEN levels may provide new ideas for the clinical diagnosis and treatment of OP high-risk patients.

During the carcinoma transformation of colitis， the imbalance of “metabolic-immune interaction” resulted from abnormal energy and metabolic substrates flow and direction was the key process， which caused by intercellular metabolic competition. Based on traditional Chinese medicine （TCM） theory and clinical research， we found that “fire failing to warm earth” is the key pathogenesis of colon-cancer transformation. “Fire” was a synonym for TCM to understand the energy metabolism， combined modern medical research findings， we thought energy metabolism disorders was a microcosmic manifestation of the “fire decline”， while abnormal immune function was the biological basis of “earth deficiency”. The imbalance between “metabolism-immune interaction” and the “fire failing to warm earth” pathogenesis of colitis-cancer transformation demonstrated the different understanding of the same pathological mechanism between western medicine and TCM. For treatment， it could be effectivce to delay the transformation of colitis-cancer by synergistically regulated the energy metabolism - “replenish fire” and enhanced the immune function - “nourish earth”， which was called the methods of replenishing fire to nourish earth.

Pulmonary nodule is a key window for moving ahead the diagnosis and treatment of lung cancer. Traditional Chinese medicine （TCM） can delay the transformation of lung nodules into lung cancer， improve the prognosis of patients， effectively fill the treatment gap during the follow-up period of pulmonary nodules， and has been applied it in the whole cycle and multi-dimensional management of pulmonary nodules. This paper discussed the construction ideas and feasible paths of the whole process management diagnosis and treatment system of pulmonary nodules in TCM， proposed the diagnosis and treatment database of TCM for pulmonary nodules based on the social module of “family-community-hospital”. Through artificial intelligence， we can develop， improve and promote the multi-level and multi-modal “disease-symptom combination” risk prediction model and effectiveness evaluation system of pulmonary nodules. At the same time， the biological connotation of the prevention and treatment of pulmonary nodules by TCM is excavated， which provided empirical evidence for the construction of TCM diagnosis and treatment system， in order to further improve the quality and diagnosis and treatment level of the whole course management of pulmonary nodules.

Objective:To study the prognostic impact of prognostic nutritional index (PNI) before radiotherapy in clinical stage Ⅲ esophageal cancer patients.Methods:We retrospectively reviewed 125 esophageal cancer patients with clinical stage Ⅲ undergoing definitive radiotherapy in Fourth Hospital of Hebei Medical University from 2013 to 2017. The PNI and nutritional risk index (NRI) were calculated before radiotherapy. The optimal cutoff value of PNI was determined by time-dependent receiver operating characteristics (ROC) at 49.925.The patients were divided into low PNI group(PNI<49.925) and high PNI group (PNI≥49.925). Based on NRI, the patients were divided into normal NRI group (NRI≥100) and abnormal NRI group (NRI<100). Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS) and to perform univariate analysis. The mutlivariate analysis was performed by Cox regression model.Results:PNI was positively correlated with hemoglobin ( r=0.505, P<0.001) and NRI ( r=0.594, P<0.001). The 1-, 3- and 5-year OS rates in the low PNI group were significantly lower than those of the high PNI group (67.5%, 27.3%, 11.4% vs. 85.4%, 45.8%, 27.4%, respectively, χ2=8.569, P<0.05). Moreover, the 1-, 3- and 5-year PFS rates in the low PNI group were obviously higher than those in the high PNI group (59.7%, 23.2%, 4.9% vs. 79.2%, 35.4%, 24.9%, respectively, χ2=6.715, P<0.05). Univariate analysis showed that GTV, radiotherapy dose, chemotherapy, albumin, NRI and PNI were significantly correlated with OS and PFS (OS: χ2=6.822, 4.326, 4.474, 13.123, 8.846, 8.569, P<0.05: PFS: χ2=7.869, 4.636, 5.874, 10.911, 8.544, 6.715, P<0.05). Multivariate analysis showed that GTV, radiotherapy dose and PNI were independent prognostic factors for OS ( P<0.05). And GTV, radiotherapy dose, chemotherapy and PNI were independent prognostic factors for PFS ( P<0.05). Conclusions:The PNI before radiotherapy is a significant and independent predictor for survival of clinical stage Ⅲ esophageal cancer patients. Based on simple and inexpensive standard laboratory measurements, PNI could be a promising prognostic biomarker for esophageal cancer patients.

Objective: To investigate the relationship between the expression of RNA-binding protein 38 (RBM38) and distant metastasis and prognosis of breast cancer. Methods: A total of 161 cases of breast cancer tissues were selected, and the expression of RBM38 was detected by immunohistochemical SP method. The relationship between the expression of RBM38 and the distant metastasis and prognosis of breast cancer patients were analyzed. Cox regression model was applied to analyze the influence factors of distant metastasis of breast cancer. Results: Among the 161 breast cancer patients, high expression of RBM38 was observed in 85 cases and low expression was observed in 76 cases. Log rank test showed that the distant metastasis rate of RBM38 highly expressed group was significantly lower than that of RBM38 lowly expressed group (P=0.010), while the survival rate was significantly higher (P=0.009). Univariate Cox regression analysis showed that the pathological stage (P=0.001), axillary lymph node positive (P=0.001), and the expression of RBM38 (P=0.015) were dramatically related to the distant metastasis of breast cancer patients. Multivariate Cox regression analysis showed that positive axillary lymph node was an independent risk factor (RR=4.222, 95% CI: 1.235-14.432), and high expression of RBM38 was an independent protective factor (RR=0.328, 95% CI: 0.128-0.839) of distant metastasis of breast cancer patients. Conclusion High expression of RBM38 is positively related with low distant metastasis rate and good prognosis of breast cancer patients. Hence, high expression of RBM38 is an independent protective factor of distant metastasis.

Objective To explore the risk factors of gestational diabetes mellitus and its influence on pregnancy outcome,and to provide guidance for early intervention of gestational diabetes to improve pregnancy outcome in clinic.Methods Totally 159 patients with gestational diabetes mellitus in our hospital from January 2014 to January 2016 as observation group were collected,and at the same time,634 healthy pregnancy women as control group were collected.The risk factors of gestational diabetes mellitus were analyzed by the Logistic regression analysis and comparison of pregnancy outcome between two groups was conducted.Results The patients in the observation group with age ≥ 35 years,overweight or obesity before pregnancy,adverse pregnancy history,family history of diabetes,hypertension and vaginal candida and thyroid peroxidase antibody (TPOAb) compared with the control group,the difference was statistically significant (P ＜ 0.05).Multivariate logistic regression analysis showed that age ≥ 35 years,overweight or obesity before pregnancy,adverse pregnancy history,family history of diabetes,and positive TPOAb were the independent risk factors of gestational diabetes mellitus,OR was 2.441,2.889,1.486,4.879,and 1.323,respectively;the difference was statistically significant (P ＜ 0.05).The incidence of premature rupture of membrane,pregnancy hypertensive disorder,premature birth,polyhydramnios,uterine-incision and postpartum hemorrhage in observation group were higher than those in control group,the difference was statistically significant (P ＜ 0.05).The incidence of giant baby,fetal distress and mild neonatal asphyxia were higher than those in control group,and the difference was statistically significant (P ＜ 0.05).No statistical significance in fetal growth restriction,neonatal malformations between two groups was found (P ＞ 0.05).Conclusions Age ≥35 years,overweight or obesity before pregnancy,adverse pregnancy history,family history of diabetes,and thyroid dysfunction were the independent risk factors of gestational diabetes mellitus,and it has serious effect on pregnancy outcome,so that it should take measures to prevent the independent risk factors.

Objective To analyze the thickness of cornea and corneal epithelium in healthy subjects by optical coherence tomography angiography (OCTA).Methods Totally 100 healthy subjects aged between 20 and 30 years were analyzed by OCTA technique.Using AngioVue OCTA system of retinal imaging mode,and using SSADA algorithm for imaging,the cornea and the corneal epithelium in the central corneal diameter range of 9 mm were measured.The differences of corneal and corneal epithelial thickness in different gender regions were compared.Results In the male and female group,the corneal central total thickness were (559.92 ±33.26) μm and(540.06 ±31.63)μm,and the corneal epithelial thickness were(57.78 ±4.88) μm and(56.88 ±4.57) μm,The total central corneal thickness and central corneal epithelial thickness of the male were greater than those of the female,the difference was statistically significant (t =3.06,2.10;all P ＜ 0.05).The cornea of male was the thickest at S5,S7 and SN9,there were significant differences at S5 and S7 compared with female (t =2.93,2.83;all P ＜ 0.05);The female cornea was the thickest at S5,SN7 and SN9,and the difference was significant at S5 compared with male.The cornea of male subjects was the thinnest at IT,which was statistically significant only at IT5 compared with female subjects in the same area (t =2.02,P ＜ 0.05);The cornea of female subjects was the thinnest at T5,IT7 and T9,which was statistically significant only at T5 and T9 compared with male subjects in the same region (t =2.63,2.20;all P ＜ 0.05);There was significant difference in corneal thickness between male and female at ST (t =3.1 1,2.79,2.33;all P ＜ 0.05).The corneal epithelium was the thickest at IT5,I7,and I9,and the lowest at S5,S7 and S9,and there was no significant difference compared with female in the same region (all P ＞ 0.05).The corneal epithelium of female at the IT5,T7,N9 were the thickest,SN5,S7,S9 were the thinnest;Except for M2 and SN5,there was no significant differences in corneal epithelium between male and female groups (all P ＞ 0.05).Corneal central epithelium accounted for the largest percentage of total corneal thickness,and gradually decreased from inside to outside.Conclusion OCTA can be used to measure the thickness of corneal and corneal epithelial regions.

Objective To explore the effects of amniotic lacrimal duct stenting on the prevention of dry eye in castrated rabbits.Methods Thirtysix healthy male rabbits were selected,the third eyelid were cut off and antiinfection treatment were given,which were randomly divided into 3 groups (12 cases in each group),the castrated male rabbits models were made.Among them,group A was negative control group,group B was dry eye model group,group C was group of lacrimal amniotic membrane group.At 2 weeks before implantation of amniotic lacrimal duct stent,2 weeks,4 weeks and 6 weeks after implantation,the fluorescent (FL) examination,Western blot,Schirmer I examination,immunofluorescence staining and corneal confocal microscopy were performed.Results The levels of tear secretion and FL in the three groups among different time points were significantly different (F=7.126,P =0.009;F =9.658,P =0.016),and there were significant differences among three groups (F =12.582,P =0.005;F =13.187,P =0.013).The tendency of tear secretion and FL in the three groups were also significantly changed (F =8.531,P =0.007;F =10.652,P =0.019).The epithelial basal cells at 6 weeks after implantation in three groups were 3811 ±414,3820 ± 314,2789 ± 353,and the density of inflammatory cells was 266 ±28,266 ± 29,67 ± 13,there were significant differences among three groups (F =13.442,P =0.012;F =9.231,P =0.021).The K1 6 staining in the duct epithelium were negative,and the expression of α-SMA in the lacrimal duct tissue of group A,B and C was not changed at all time points after implantation of amniotic lacrimal stent,and there was no significant difference (F =14.681,P =0.002).Conclusion The amniotic lacrimal stent implantation has certain effect on the prevention of dry eye in rabbit.

BACKGROUND:Regulatory T cels (Treg) are classified into two subsets, nature Treg (nTreg) and induced Treg (iTreg). Although there is consensus that CD4+CD25+FoxP3+CD127-is the widely accepted phenotype of Treg, it remains unclear what is the difference in phenotypes including cytokine patterns of nTreg and iTreg. OBJECTIVE:To understand and compare the plasticity of nTreg and iTreg and to search the exact mechanism of cytokine secretion in Tregs. METHODS: We investigated the frequency and cytokine pattern of CD4+CD25+FoxP3+CD127-nTreg in freshly separated peripheral blood mononuclear cels of five healthy individuals using 8-color fluorescence flow cytometry (FACSCanto II). Subsequently, after 9 days of alostimulation in mixed lymphocytes, the frequency and cytokine pattern of CD4+CD25+FoxP3+CD127-iTreg were determined and analyzed. RESULTS AND CONCLUSION:In fresh cels, (1.5±0.70)% of CD4+ T cels were CD4+CD25+FoxP3+CD127- nTregs. Almost al these cels expressed interferon (IFN)-γ-, interleukin (IL)-2- or transforming growth factor-β+, and partial cels expressed IL-10+ or IL-10-. After 9-day alostimulation, the number of CD4+CD25+FoxP3+CD127- iTreg expressing IFN-γ+, IL-2-, IL-2+, IL-10+ or TGF-β+increased strongly. The main subsets of human nTregs were CD4+CD25+FoxP3+CD127-IFN-γ-IL-2-IL-10+TGF-β+and CD4+CD25+FoxP3+CD127-IFN-γ-IL-2-IL-10-TGF-β+ T cels. The proportion of each subset in CD4+ T cels was (1.1±0.59)% and (0.39±0.16)%, respectively. Whereas the main subsets of human iTregs were CD4+CD25+FoxP3+CD127-IFN-γ+IL-2-IL-10+TGF-β+ and CD4+CD25+FoxP3+CD127-IFN-γ+IL-2+IL-10+TGF-β+. Human nTregs were characterized as IFN-γ-IL-2- double negative, producing IL-10 and TGF-β or only TGF-β without IL-10, and not proliferatingin vitro. During the alostimulation in mixed lymphocytes, IFN-γ+ iTregs proliferated remarkably. One-third of IFN-γ+ iTreg expressed IL-2+, and two-thirds of IFN-γ+ iTregs expressed IL-2, both of which produce IL-2 and TGF-β. Our results imply that CD4+CD25+FoxP3+CD127- Treg are potentialy immunosuppressive probably because of their mandatory TGF-β and optional IL-10 production.